Amide and Peptide Bond Formation in Water at Room Temperature

Abstract

A general and environmentally responsible method for the formation of amide/peptide bonds in an aqueous micellar medium is described. Use of uronium salt (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as a coupling reagent, 2,6-lutidine, and TPGS-750-M represents mild conditions associated with these valuable types of couplings. The aqueous reaction medium is recyclable leading to low E Factors.

Library of Norcoclaurine Synthases and Their Immobilization for Biocatalytic Transformations

“…After filtration, the white solid was identified as N ‐(3,4‐dimethoxyphenethyl)‐2‐phenylacetamide (320 mg, 1.07 mmol, 53%), rf = 0.51 (silica, hexanes: ethyl acetate 3:7). Mp = 106–108 °C (lit: 108–109 °C), the NMR data was in accordance with the literature . 1 H NMR (300 MHz, CDCl 3 ) δ 7.33–7.10 (m, 3H), 7.10–6.99 (m, 2H), 6.59 ( d , J = 8.1 Hz, 1H), 6.51–6.36 (m, 2H), 5.24 (s, 1H), 3.73 (s, 3H), 3.69 (s, 3H), 3.41 (s, 2H), 3.32 (dd, J = 12.8, 6.8 Hz, 2H), 2.55 ( t , J = 6.9 Hz, 2H).…”

Indole–Indole Ullmann Cross‐Coupling for CAr–N Bond Formation: Total Synthesis of (–)‐Aspergilazine A

“…Cleavage of the Boc protecting groups by using TMSI led quantitatively to the C6–N1′ bis‐tryptophan, which was not isolated. Double condensation of this intermediate with N ‐Boc‐protected l ‐proline 25 in Lipshutz's aqueous micellar medium of 2 % TPGS‐750‐M with (1‐cyano‐2‐ethoxy‐2‐oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as the coupling agent afforded desired tetrapeptide 26 in 75 % combined yield. Finally, silica‐gel‐assisted thermal removal of the two Boc groups took place concomitantly with twofold DKP formation to afford (–)‐aspergilazine A ( 4 ) in quantitative yield.…”

Making Solid‐Phase Peptide Synthesis Greener: A Review of the Literature

“…COMU was also used for amide bond formation and for the synthesis of dipeptides in the presence of TPGS‐750‐M, a designed surfactant that when dissolved in water assembles into nanomicelles . The authors reported the synthesis under environmentally benign conditions such as using water as the solvent, with an improved E factor, and the recyclability of the reaction medium.…”

“…The authors reported the synthesis under environmentally benign conditions such as using water as the solvent, with an improved E factor, and the recyclability of the reaction medium. Additionally, coupling using COMU led to no racemization, thus making it an efficient protocol …”